This phase I trial is studying the side effects and best dose of sunitinib when given together with cetuximab and radiation therapy in treating patients with locally advanced or recurrent squamous cell carcinoma of the head and neck. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving sunitinib together with cetuximab and radiation therapy may kill more tumor cells.

Intervention Model: Single Group AssignmentMasking: Open LabelPrimary Purpose: Treatment

Official Title:

A Phase I Trial of Concurrent Chemoradiation/Chemoreirradiation With Cetuximab (ERBITUX®), Sunitinib, and Accelerated Radiation in Patients With Locally Advanced/High-risk/Recurrent Poor Prognosis Head and Neck Cancer

MTD is defined as the dose level immediately below the non-tolerated dose. The study will utilize a standard "3+3" design to determine the MTD. Dose limiting toxicities (DLTs) used for determining escalation of dose will be those occurring within the period of radiotherapy. Toxicity will be summarized by type and severity using the National Cancer Institute (NCI) Common Terminology Criteria.

Secondary Outcome Measures:

Objective tumor response rates [ Time Frame: From the start of the treatment to up to 6 years ] [ Designated as safety issue: No ]

Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The efficacy analysis population (an exploratory analysis of those patients on study for the MTD) will consist of all subjects who received at least 1 dose of sunitinib. Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

Locoregional control rates [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

Disease control rates [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

Ninety percent confidence intervals using the exact binomial distribution will be presented. Kaplan-Meier product limit curves will be calculated.

Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.

Drug: sunitinib malate

Given orally or by percutaneous gastrostomy tube

Other Names:

SU11248

sunitinib

Sutent

Other: pharmacological study

Correlative studies

Other Name: pharmacological studies

Radiation: 3-dimensional conformal radiation therapy

Undergo radiotherapy

Other Names:

3D conformal radiation therapy

3D-CRT

Biological: cetuximab

Given IV

Other Names:

C225

C225 monoclonal antibody

IMC-C225

MOAB C225

monoclonal antibody C225

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety, the maximum tolerated dose, and the dose limiting toxicity of sunitinib malate when administered in combination with cetuximab and radiotherapy in patients with locally advanced, recurrent, or second primary poor prognosis, high-risk squamous cell carcinoma of the head and neck.

SECONDARY OBJECTIVES:

I. To describe the toxicity profile of this regimen. II. To explore the tolerability and feasibility of sunitinib malate when administered in combination with cetuximab and radiotherapy in these patients.

III. To assess the best overall response rate (complete and partial response) after completion of treatment.

IV. To assess the locoregional control rate. V. To assess the distant control rate. VI. To assess the pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube.

OUTLINE: This is a dose-escalation study of sunitinib malate.

Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.

*NOTE: *Patients may have resection prior to enrollment on protocol provided they have high-risk features for recurrence.

Some patients undergo blood sample collection at baseline and periodically during study for pharmacokinetic analysis of sunitinib malate and metabolites.

After completion of study treatment, patients are followed up periodically for up to 6 years.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed squamous cell carcinoma of the head and neck, meeting any of the following criteria:

Recurrent disease

Second primary locoregional recurrence* with no clinically measurable distant disease

Poor prognosis non-metastatic head and neck carcinoma (M0)

Must have undergone radiotherapy as a component of prior treatment

Not a candidate for surgical resection with curative intent

Patients with high-risk features at resection or following resection for recurrence are eligible

Must have locoregional tumor amenable to radiotherapy or reirradiation with curative intent

Entire gross tumor recurrence volume must be able to be treated without exceeding a cumulative spinal cord dose of 50 Gy

Unresected tumors must be measurable according to RECIST

No known brain metastases

ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

Life expectancy > 12 weeks

WBC ≥ 3,000/mm^³

ANC > 1,500/mm³

Platelet count > 100,000/mm³

Total bilirubin < 1.5 times upper limit of normal (ULN)

INR and PTT ratio < 1.5

AST and ALT ≤ 2.5 times ULN

Creatinine normal OR creatinine clearance > 60 mL/min

Urine protein no more than trace

Hematocrit ≥ 28%

Hemoglobin ≥ 9 g/dL

QTc < 500 msec

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception

The following patients are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO and MUGA:

Asymptomatic on treatment

Prior anthracycline exposure

Prior central thoracic radiotherapy included the heart in the radiotherapy port

No clinical evidence of active infection of any type, including hepatitis B or C virus

Infections controlled with therapy are allowed

Patients with hepatitis B or C on antiviral therapy with no detectable virus are allowed

No immune deficiency and/or HIV positivity

No history of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate

No gastrointestinal tract disease or condition, including any of the following, that impairs ability to retain sunitinib tablets:

Inability to take oral medication or a requirement for IV alimentation

Prior surgical procedures affecting absorption

Active peptic ulcer disease

None of the following conditions allowed:

Serious or nonhealing wound, ulcer, or bone fracture

Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days

No significant concurrent medical or psychiatric illness which, in the opinion of the investigator, would interfere with the patient's ability to participate in the trial

No active carotid artery involvement

No history of documented thrombosis (pulmonary embolism within the past 12 months or deep vein thrombosis [DVT] within the past 6 months), known coagulopathies or thrombophilia, or evidence of DVT/thromboembolic event

No concurrent commercial agent or therapy intended to treat head and neck cancer

No other concurrent anticancer therapy

Contacts and Locations

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For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00906360